The Role of SDF-1 Cerebral Repair Following Stroke

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DESCRIPTION (PROVIDED BY APPLICANT): Stroke is the nation's third leading cause of death and the leading cause of long-term disability. Preliminary data show that during cerebral repair, Stromal Cell-Derived Factor-1 (SDF-1) is upregulated in the brain of mice. SDF-1 is thought to be chemotactic for many cell types, and to promote angiogenesis. I hypothesize that the upregulation of SDF-1 is due to hypoxia and mediates the repair mechanisms of the brain following ischemia by inducing neovsacularization and by homing bone marrow derived cells to the site of injury leading to an overall increase in functional recovery. To test my hypothesis, I plan to: (1) determine the contribution of SDF-1 to neovascularization of the brain and determine the increase in functional recovery post-ischemia using a novel GFP chimeric mouse stroke model, (2) determine whether SDF-1 induces neovascularization in vitro by upregulating angiogenesis or by upregulating vasculogenesis, (3) investigate whether the upregulation of SDF-1 in response to hypoxia is under HIF-1 regulation in vitro. Understanding the endogenous repair mechanisms following stroke could lead to novel treatments to enhance the natural repair processes, which could decrease mortality and limit long-term disability seen in stroke patients.